A mass spectrometry (MS) system in general includes an ion source for ionizing molecules of a sample of interest, followed by one or more ion processing devices providing various functions, followed by a mass analyzer for separating ions based on their differing mass-to-charge ratios (or m/z ratios, or more simply “masses”), followed by an ion detector at which the mass-sorted ions arrive. An MS analysis produces a mass spectrum, which is a series of peaks indicative of the relative abundances of detected ions as a function of their m/z ratios. Mass spectrometers are commonly used to determine the chemical composition of mixtures by precise measurement of the mass-to-charge ratio of the constituent molecular ions.
One particular type of mass spectrometer is a time-of-flight mass spectrometer (TOF-MS), which is utilized for molecular and elemental identification within a variety of disciplines ranging from medicine, biological research, environmental monitoring, chemical manufacturing, energy, and forensics. Time-of-flight mass spectrometry (TOF-MS) offers a powerful combination of mass resolution, accuracy, speed, and mass range which together make the technique well-suited for the analytical challenges presented by these fields. TOF-MS utilizes a high-resolution mass analyzer (TOF analyzer) in the form of a flight tube, which encloses a space that is electric field-free except for localized fields imparted by devices in the flight tube such as an ion mirror. An ion accelerator (or pulser) injects ions in pulses (or packets) into the flight tube. Ions of differing masses travel at different velocities through the flight tube and thus separate (spread out) according to their differing masses before arriving at the ion detector, enabling mass resolution based on time-of-flight. In a typical TOF-MS, ions travel along a drift direction through one or more gas-filled ion guides, and one or more beam-limiting apertures operating in a collision-free environment, and into the pulsed ion accelerator. In an orthogonal acceleration TOF-MS (oa-TOF-MS), the ion accelerator receives the ions along the drift direction and injects the ions along an acceleration direction orthogonal to the drift direction. The flight tube may include one or more ion mirrors (or “reflectrons”) that increase the length of the ion flight path and provide certain advantages.
In TOF-MS, chemical composition is determined by accurately measuring the masses of individual ions drawn from the sample. The critical mass measurement stage is realized by measuring the time elapsed as ions travel from an ion accelerator through a known path length. Ions end their flight on a fast ion detector at which a single ion is transformed into a nanosecond-scale electronic signal, which is digitized with a high speed data acquisition system. The inherent simplicity and speed of this process translates into multiple analytical advantages for the end user. Because TOF-MS is able to gather a complete mass spectrum for each firing of the ion accelerator, it is particularly well-suited for tandem mass spectrometry (MS/MS) in which the fragmentation spectrum associated with a particular parent ion mass is measured.
TOF-MS is commonly used to determine the chemical composition of unknown mixtures. Mass resolution and sensitivity are two of the most fundamental and important instrument parameters when analyzing complex mixtures and identifying unknown compounds. High-resolution instruments are able to resolve two or more compounds which are closely-spaced in mass, a situation commonly found in complex mixtures in chemical and life sciences applications. Improvements to mass resolution typically also improve mass accuracy which in turn results in improved identification of unknown compounds. Since many of the compounds are present only at low concentrations, instruments which have both high sensitivity and high resolution are needed. Existing approaches to improving resolution and their disadvantages are described below. There remains an ongoing need for improving the resolution and/or sensitivity of time-of-flight mass spectrometers.